Are You More Immune to HIV Than You Thought?

For the past several decades, doctors and scientists could not understand why some people quickly get sick – and can die – when infected with HIV, while others seem to naturally resist the virus for several years with less damage done to their immune systems. Researchers at the University of Minnesota’s College of Biological Sciences and Medical School looked at the virus’s rapid-mutation ability, along with how it attacks the human immune system to replicate, and hypothesized that this distinct difference in how the virus differently affects infected individuals is somehow caused by the genetics of the infected host. In trying to understand why some are more immune to HIV than others, these researchers discovered a new crack in the HIV cell’s armor which helps explain this phenomenon.

HIV attacks the immune system in order to replicate within the infected host’s cells. It seeks out the immune system cells called T lymphocytes (T cells), and uses the cell’s molecular machinery to replicate within them, killing the cells when it is done with each cell. This infection eventually depletes the system of necessary T cells, leaving the infected host helpless to other invading viruses and bacteria. The T cells do have a defense against this, as they have an anti-virus protein in their arsenal – called APOBEC3 – which has the ability to block the HIV cell’s replication process. If they are successful, they can effectively stop the virus from replicating and eventually clear it from the system as the virus cells die off. Unfortunately, HIV has developed a counter-attack to this protein, a protein of their own – called Vif – which attach themselves to the APOBEC3 cells and trick the T cells into destroying their own protein, leaving them defenseless to the virus’s replication and destructive abilities. To learn why some seem to be able to naturally fend off the virus – at least for a lot longer than others – researchers looked closer at these proteins. They found strong clues as to why some immune systems work better against the virus than others.

Some people have a greater ability to create a version of the APOBEC3 protein, which is known as APOBEC3H. This particular form of the protein is boosted whenever someone is infected with HIV, which made the researchers believe this plays an important role in the immune system’s defense against HIV. What they found was a confirmation of this assumption, as people with a more stable accumulation of the APOBEC3H protein seem to be more naturally immune to HIV than those with a more unstable accumulation of this protein. Whenever the infecting HIV cells had a weaker version of their Vif protein (as constant mutations cause the virus to be varied in its strengths and weaknesses), the infected individual with a stable APOBEC3H protein in their T cells had a better time limiting the HIV cells from replicating. This was not the case if the infecting virus cells were equipped with a stronger Vif protein. This discovery helps scientists and doctors with a new path towards attacking HIV, with a possible road to a cure. The more we can suppress the virus’s Vif protein, the more our natural immune system has a chance to combat against the infection. Coupled with a strong antiretroviral regimen, this could help stop the virus from replicating, and possibly killing it outright.